Interfering with implantation by postcoital estrogen administration. II. Endometrium epithelial cell ultrastructure.

Secretory human endometrium was studied by electron microscopy after high-dose ethinylestradiol administration, a method used for interception (morning-after pill). Medicated (experimental) cycles were compared to non-medicated (control) cycles in the same volunteers. The nucleolar channel system typically present in the nucleus of the epithelial cell in secretory phase of the human endometrium disappears completely as a result of this treatment, resulting in a nucleolar basket structure. Glycogen deposits were prominent at the basal membrane and in the apex of the cell during the experimental cycle. Giant mitochondria were observed to occur to similar extent during control and treatment cycles. This study confirms the morphological delay found in light microscopic studies, published earlier with diethylstilbestrol and with ethinylestradiol.

PIP: High-dose ethinylestradiol is used as a postcoital contraceptive. Its mechanism of action is to delay the secretory development of the endometrial epithelial cells. This study, using 4 normal volunteers, was undertaken to see the effects of high-dose ethinylestradiol on the ultrastructure of the endometrial cells and on glycogen metabolism during the luteal phase of the menstrual cycle. Ovulation was determined from plasma luteinizing hormone levels, and the subjects were given 5 mg ethinylestradiol for 5 consecutive days thereafter. The nucleolar channel system, which typically appears in the cell during the secretory phase, completely disappeared after treatment with ethinylestradiol. Moreover, the Golgi complexes were enlarged, and large amounts of glycogen accumulated at the basal membrane and in apical vacuoles of the cells. These changes show that large doses of ethinylestradiol given after ovulation interfere with the synthesis and secretion of glycogen in the endometrial epithelial cells.

Postcoital interception with steroids.

At present there is a high demand for PCI. The psychological distress experienced by women after unprotected intercourse while awaiting the onset of her next menses could be avoided with effective postcoital treatment. As demonstrated in countries with good health services, the availability of PCI leads to low abortion rates. PCI is designed for use as an emergency method after unprotected intercourse as an isolated incident. Women who have frequent intercourse however, do better to use a regular, very effective, method of contraception such as a combined oral contraceptive. Postcoital progestagens can well be used in infrequent intercourse since they are to be taken after each coitus, if applicable several times a month. Such use however leads to menstrual cycle disturbances and irregular bleedings. The estrogen-only and the estrogen-progestin combination are recommended, but need to be given within 2 or 3 days after the event of unprotected intercourse, preferably periovulatory. The latest development of the anti-progestins as a morning-after pill is promising. Taken from day 27 through 30 of the menstrual cycle it induces menstruation at the expected day. Side effects are minimal and the efficacy is good. Because of the imperfectness of PCI to prevent all pregnancies, sofar this regimen cannot be recommended for monthly use and does not replace regular oral contraceptives. PCI has a definite place in family-planning and fertility regulation. Since different methods are available today careful assessment of individual needs can help to decide for the best suitable method for the individual person.

Interception. III: Postcoital luteal contragestion by an antiprogestin (mifepristone, RU 486) in 62 women.

The new antiprogestin mifepristone (RU 486) was studied as an emergency postcoital contragestive. An actual pregnancy rate of 1.6% was observed and was related to the actual conception rate. The follow-up rate was 100%. The patterns of onset and duration of the induced menstruation after mifepristone treatment are described. This method provides a good new interceptive technique when the time for use of postcoital steroids or for a postcoital IUD insertion has lapsed.

Interception. IV: Failure of mifepristone (RU 486) as a monthly contragestive, "Lunarette".

The new antiprogestin mifepristone (RU 486) was studied as a contragestive for continuous fertility control in 24 menstrual cycles. Two pregnancies out of three conceptions continued in spite of antiprogestin treatment. To date, mifepristone at the doses used appears to be inadequate for monthly use.

Post coital contraception.

PIP: The experience of the Utrecht State University with postcoital estrogens in high and low combined doses and with postcoital placement of IUDs since 1964 with over 4000 patients is summarized. The high dose postcoital estrogen treatment consists of 5 mg ethinyl estradiol for 5 days, either orally, or in case of vomiting not controlled by an antiemetic, estradiol benzoate 30 mg by injection. Side effects recorded in 3016 women were nausea in 54%, vomiting in 24%, tender breasts in 23%, menorrhagia in 11%, altered cycle length in 24%. Complications were 1 case of non-fatal pulmonary edema and 1 case of an 8 kg weight gain during treatment. There were 3 pregnancies. The overall failure rate in the whole series was 0.15%, with 10% ectopic pregnancies. There were no thromboembolisms or teratogenic effects. The combined estrogen treatment consisted of 50 mc ethinyl estradiol with 250 mc levonorgestrel (Neogynon oral contraceptive), 2 pills followed by 2 pills 12 hours later. A double-blind randomized trial resulted in no significant differences in pregnancy rates or side effects between the high and low dose regimens. The alternate treatment, if the woman presents more than 72 hours after intercourse, or if estrogens are contraindicated, is postcoital insertion of an IUD. The Dept. of Obstetrics and Gynecology does not place an IUD in a woman with infection nor in case of rape unless there is time for a complete work-up. Nulliparas are informed of the increased risk of pelvic inflammatory disease. Recently, the Multiload-copper 250 and later ML 375 were used exclusively, to achieve better blastocidal effect and lower expulsion rates. The ethical debate over use of postcoital methods centers around the morality of "procuring a miscarriage," but this argument is not relevant since these methods will not terminate a pregnancy once implantation has occurred. In the Netherlands, 25% of all abortion clients become pregnant during their 1st intercourse. In 1982, 35,000 postcoital contraceptives were administered, (roughly 16% of all pregnancies), compared to 15,000 abortions (7% of pregnancies; a total of 23% of pregnancies terminated). Compare these figures with 29% unwanted pregnancies all terminated by abortion in Sweden in that year. The postcoital methods are cheap, effective, and invaluable in emergency cases of rape, incest, intoxication, failure of barrier contraceptives, or unwanted pregnancy in women fearful or opposed to abortion.^ieng

Interception II: postcoital low-dose estrogens and norgestrel combination in 633 women.

The new low-dose hormonal postcoital method, a combination of 200 mcg ethinylestradiol and 2 mg norgestrel was used in 633 women, and a statistically significantly lower observed pregnancy rate was found compared to the expected number of pregnancies if no contraception was used. Patterns of menstruation, its onset and duration, after use of this morning-after pill, are documented in respect to follicular, midcycle and luteal administration. Individual side effects such as nausea, vomiting and mastalgia are noted, but antiemetics did not reduce the incidence. Though efficacy of this technique is not found to be favorable in comparison to the 5 mg ethinylestradiol treatment, the low-dose of steroid, the one-day treatment and its lesser side effects show this alternative morning-after pill suitable for use as a first choice in case of an unprotected sexual encounter.

A comparison of high-dose estrogens versus low-dose ethinylestradiol and norgestrel combination in postcoital interception: a study in 493 women.

Ethinylestradiol (EE), at a dosage of 5 mg/day for 5 consecutive days (5 mg EE), has generally been used for interception. A combination of 200 micrograms EE and 2 mg dl-norgestrel (EE + NG) was proposed as an effective alternative. Efficacy and tolerance of these methods were compared in a randomized, double-blind study. A group of 465 women was studied with a follow-up rate of 94.3%. In the 5 mg EE group a pregnancy rate of 0.9% was observed, and in the EE + NG group a rate of 0.4% was found. These rates differ significantly from the expected rates (P less than 0.0005, in both series). Nausea was noted in 59.1% of the 5 mg EE group and in 54.0% of the EE + NG series. Nausea and vomiting occurred in 20.8% and 15.8%, respectively. The efficacy of both methods as alternative morning-after medication was confirmed. The new method is preferable because treatment is limited to only 1 day.

PIP: Ethinyl estradiol (EE), at a dosage of 5 mg/day for 5 consecutive days (5 mg EE) has generally been used for interception. A combination of 200 mcg EE and 2 mg dl--norgestrel (EE+NG) was porposed as an effective alternative. Efficacy and tolerance of these methods were compared in a randomized, double-blind study. A group of 465 women was studied with a follow-up rate of 94.3%. In the 5 mg EE group, a pregnancy rate of 0.9% was observed, and in the EE+NG group, a rate of 0.4% was found. These rates differ significantly from the expected rates (P0.0005, in both series). Nausea was noted in 59.1% of the 5 mg EE group in and 54.0% of the EE+NG group. Nausea and vomiting occurred in 20.8% and 15.8% respectively. The efficacy of both methods as alternative to morning-after medication was confirmed. The new method is preferable since treatment is limited to only 1 day.

[Postcoital IUD insertion, a review]. / Postkoitale IUP-Einlage, ein Uberblick.

Following the development of hormonal interception after coitus the post-coital insertion of an intrauterine contraceptive device was proposed by Tatum . The advantage of this treatment is the avoidance of the ingestion of large doses of estrogen which causes much nausea and vomiting although it is a very effective post-coital method of contraception. The recently proposed alternative administration of 200 micrograms Ethynol Estradiol combined with 2 mg of DL norgesterol in 2 equal doses at 12 hour intervals has the same disadvantage of a high percentage of side effects. The post-coital insertion of an intrauterine contraceptive device is the first method which is effective up to five days following unprotected intercourse which is three days longer than treatment by estrogen. In addition the method can be offered to women who would want to continue to wear the intrauterine contraceptive device for long term contraception. The disadvantage of the post-coital insertion of an intrauterine contraceptive device is the ability of serious complications if the patient has a vaginal or venereal infection or an asymptomatic cervicitis or salpingitis. Following appropriate physical examination women who present themselves for post-coital treatment are selected. Cases of rape are usually not suitable for treatment with intrauterine contraceptives devices. However, when cases of rape are seen early enough the appropriate investigations may be done and the treatment with the intrauterine device started within five days. The potential risk of future infertility must be considered since salpingitis is 7 times more common in nulliparous wearers of intrauterine devices than in nulliparous non-wearers. Young sexually active nulliparous women especially of lower socio economic background are patients with a high risk. Over 70% of the women who present themselves for interception treatment are nulliparous.(ABSTRACT TRUNCATED AT 250 WORDS)

[Contraception by post-coital IUD insertion]. / Contraception par D.I.U. post-coital.

After the development of postcoital hormonal interception, the postcoital use of IUDs to prevent pregnancy was proposed by Tatum. The major advantage of this treatment is that it avoids the use of the usual massive doses of estrogens (a very effective postcoital method) which is associated with nausea and vomiting. This is the 1st method to be effective up to 5 days after exposure, 3 days more than the estrogen treatment. It may also provide long-term contraception in women who wish to continue using the IUD.

Interception by post-coital IUD insertion.

After the development of postcoital hormonal interception, the postcoital use of IUDs to prevent pregnancy was proposed by Tatum. The major advantage of this treatment is that it avoids the use of the usual massive dose of estrogens (a very effective postcoital method) which is associated with nausea and vomiting. This is the 1st method to be effective up to 5 days after exposure, 3 days more than the estrogen treatment. It may also provide long-term contraception in women who wish to continue using the IUD. A major disadvantage of postcoital IUD use is that IUD insertion can produce serious complications if a patient has a vaginal or venereal infection or an asymptomatic cervicitis or even pelvic inflammatory disease (PID). After proper physical examination, suitable patients are selected from those requesting postcoital treatment. Cases involving rape are mostly excluded from these services; but, if they present early, proper work up and treatment can be performed within the time span of 5 days available for this method and it will still be possible to fit a postcoital IUD. The potential risk of future infertility should be considered as PID rates in nulliparous IUD users are up to 7 times higher than in nonusers. Young nulliparous, sexually active women--especially of the lower socioeconomic strata--are identified as high-risk patients. Over 70% of women requesting interception are nulliparous. Clients asking for postcoital insertion should be informed of its potential risk, as women under 25 years of age are more prone to infection. The risk of septic abortion exists if an IUD is inserted into a gravid uterus due to pregnancy resulting from unreported previous sexual intercourse. Septic abortion is a life-threatening condition. Out of several series, no pregnancies are reported in the month of treatment. The IUD preferred is the Multiload copper IUD or the copper T; the highest expulsion rate proved the Copper-7 Gravigard (Cu-7) inefficient. In suitable circumstances, the IUD can be the 1st choice in postcoital interception.